tbuckley/cabot-search huggingface dataset:
Prognostic role of a novel clinical-nutritional index in pancreatic ductal adenocarcinoma: The Pancreatic Adenocarcinoma Nutritional-Clinical Index (PANCIN).
Authors: Giulia Orsi, Martina Abati, Diego Palumbo, Maddalena Pavarini, Alice Burini, Sara Cardellini, Marina Macchini, Martina Mori, Claudio Fiorino, Umberto Peretti, Maria Maddalena Valente, Anna Maria Militello, Maria Assunta Briccolani, Roberto Mele, Massimo Falconi, Stefano Cascinu, Gabriele Capurso, Michele Reni
Journal: Journal of Clinical Oncology (2023)

697 Background: Impaired nutritional status is often associated with Pancreatic Ductal Adenocarcinoma (PDAC) and poor prognosis. Little is known on the prognostic role of nutritional variables in PDAC patients (pts) receiving chemotherapy (CT). Methods: Locally advanced or metastatic PDAC pts enrolled at our Institute in a prospective observational study (PAC-MAIN) and treated with 1 st -line CT between April 2019 and July 2021 were included in the analysis. Clinical and nutritional variables entailed biohumoral parameters, bioimpedance vector analysis (BIVA)- and Computed Tomography-derived body composition. Progression-free and Overall survival (PFS and OS) were calculated from CT start to progression or death. A Multivariate Cox proportional-hazards model for PFS prediction was generated by backward selection of features with a p-value (p) ≤ 0.06. The resultant index, named PANCIN, was calculated as linear combination of the covariates (X i are the N) and the b Cox coefficients (b i ), according to the formula: PANCIN = ∑ N i=1 b i X i Kaplan–Meier test was performed to assess the ability of PANCIN to stratify pts according to its median value for PFS and OS prediction. Results: 74 pts were included in the study. The variables retained in the model were: serum Vitamin B12 (pg/ml) [Hazard Ratio (HR)= 1.001, 95% Confidence Interval (CI) 1.0004-1.0016, p=0.002]; BIVA-derived Body Cell Mass (%) [HR= 0.94, 95% CI 0.887-1.002, p=0.058]; ECOG Performance Status (0 vs 1-2) [HR= 3.25, 95% CI 1.048-10.077, p=0.041]; Albumin (g/L) [HR= 0.91, 95% CI 0.86-0.97, p=0.002]; FAACT Score [HR= 1.041, 95% CI 1.006-1.077, p=0.022]. Median PFS was 15.3 (95% CI 7.6-21.8) and 5.8 months (95% CI 2.7-9.0) for pts with PANCIN &lt; or ≥ -1.7768 median value respectively [HR= 3.7, 95% CI 1.9-7.0, p=0.0001]. Median OS was 23.8 (95% CI 12.6-33.3) and 10.0 months (95% CI 5.7-12.7) for pts with PANCIN &lt; or ≥ -1.7768 respectively [HR= 4.1, 95% CI 2.1-7.9, p&lt;0.0001]. Conclusions: PANCIN is a novel nutritional-clinical index able to predict outcome of advanced PDAC pts receiving CT. If furtherly validated, it may represent a stratification tool both in clinical practice and in prospective trials. Our findings also support the relevance of a baseline comprehensive nutritional assessment, to define tailored nutritional interventions.[Table: see text]
IL-1β and IL-6 as predictors of ypN and early response to neoadjuvant chemotherapy in patients with locally advanced GC and GEJ cancer.
Authors: Katarzyna Marcisz-Grzanka, Małgorzata Fuksiewicz, Beata Urszula Kotowicz, Paulina Wieszczy, Maria Małgorzata Kowalska, Mariola Winiarek, Jakub Pałucki, Tomasz Olesiński, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2023)

454 Background: Perioperative chemotherapy remains a standard of care in locally advanced gastric cancer. About 10-15% patients do not respond to such therapy and there are currently no biomarkers which could be used to predict early response to the neoadjuvant treatment. Methods: This prospective biomarker study aimed at identification of serum biomarkers of early response to neoadjuvant chemotherapy. Here we report only the results for serum cytokine assessments. It was an academic, nonrandomized, prospective study, conducted in MSCNRIO. Between January 2018 and November 2019 we analysed 42 patients aged 30-77 (median 63 years, 52.5% male and 47.5% female) with histologically confirmed GC or GEJ cancer qualified by MDT for perioperative FLOT. Exclusion criteria were: inflammatory and autoimmune diseases, other cancers, chronic steroid and immunosuppressive therapy. Blood sample was collected a.c. prior to the administration of cycle one (C1), two (C2) and three (C3) FLOT regimen. Serum levels of IL-1β and IL-6 were measured twice using ELISA. Results: All patients with pre-treatment IL-1β levels above 0.5 ng/ml on the postoperative histopathological report had positive lymph nodes (ypN+). There was a statistically significant difference in the level of IL-1β in the blood serum of patients before the start of treatment in the subgroups ypN0 vs ypN+ vs unresectable tumor (p = 0.003), ypN0 vs ypN+ (p = 0.002) as well as ypN+ vs unresectable tumor (p = 0.075). There was a trend for change in IL-1β level between cycles C1 and C3 in the ypN0 vs ypN+ subgroups (p = 0.056). The difference in IL-1β level before C1 between the groups TGR-G1-2/ypN0 vs TGR-G1-2/ypN+ vs TGR-G3/ypN0 vs TGR-G3/ypN+ was statistically significant (p = 0.017). The difference in IL-6 level between C3 and C1 in the subgroups TGR-G1-2/ypN0 vs TGR-G1-2 / ypN + vs TGR-G3 / ypN0 vs TGR-G3 / ypN + vs unresectable tumor was statistically significant (p = 0.009). Among the analyzed factors, only the difference in serum IL-6 level between C3 and C1 may be a predictor of ypN+ response to preoperative FLOT regimen. Among ypN0 patients, 76% had an IL-6 difference between C3 and C1&gt; 1.1, i.e. C3 greater than C1 by at least 1.1 (specificity), and among ypN+ patients 83% had an IL-6 difference between C3 and C1 &lt;1.1 (specificity). Conclusions: Low IL-1β levels before starting treatment is a prognostic factor while an early decrease in IL-6 could be considered a predictive marker of response to FLOT.
Nomogram to predict peritoneal dissemination in gastric cancer.
Authors: Prasanth Penumadu, Pavneet Kohli, Biswajit Dubashi, Sachit Ganapathy
Journal: Journal of Clinical Oncology (2023)

465 Background: Peritoneal metastasis is a poor prognostic factor in patients with gastric cancer and cannot be predicted, that can tailor oncological treatment. We retrospectively analyzed the clinicopathological data among 110 gastric cancer patients. Methods: Univariate logistic regression was performed with peritoneal disease as the outcome to assess potential risk factors associated with it. We found that age, gastric outlet obstruction, VEGF, Ki67, p53 and NLR ratio were significant factors associated with peritoneal disease. Using multiple logistic regression, the adjusted odds ratio and 95% confidence interval were estimated. The predictive accuracy of this regression model was estimated using ROC curve analysis and Area under the curve, sensitivity and specificity were estimated. A nomogram was plotted based on the regression coefficient for the prediction of peritoneal disease. Results: It was estimated that age less than 40 years had 0.19 (0.05, 0.79), GOO positive had 2.04 (0.69, 6.03), VEGF positive had 4.69 (1.79, 12.33), elevated Ki67 had 3.94 (1.55, 9.97), positive p53 had 0.43 (0.17, 1.11) and NLR ratio had 1.15 (0.88, 1.51) odds of having peritoneal disease from multiple logistic regression. The regression model had significant goodness of fit for the data (Hosmer-Lemeshow test P value &lt; 0.001). On estimating the AUC from the ROC curve for the model, we found that it had a good discriminatory ability with AUC = 0.81. Sensitivity was estimated to be 71.15%, whereas specificity was estimated to be 72.41% for the model. Subsequently, a nomogram was plotted based on the regression estimated from this model. Conclusions: The nomogram could risk-stratify those at risk of developing peritoneal disease and modify therapeutic strategies like selecting patients for prophylactic intraperitoneal chemotherapy or other novel therapeutic strategies. However, the nomogram needs to be validated prospectively.
Comprehensive characterization of <i>KRAS</i> mutations and inter-relation with primary tumor location in colorectal cancers.
Authors: Mohamed E. Salem, Scott Kopetz, Josep Tabernero, Frank A. Sinicrope, Myriam Chalabi, Jeanne Tie, Kunal C. Kadakia, Thomas J. George, Elizabeth Mauer, Lisa Macera, Calvin Y. Chao, Sara Lonardi, Eric Van Cutsem, Thierry Andre, Michael J. Overman
Journal: Journal of Clinical Oncology (2023)

231 Background: The recent development of KRAS G12C inhibitors underscores the potential to target KRAS mutations. Right-sided and left-sided colon tumors (RT and LT) exhibit different molecular features. We characterize the prevalence of KRAS-variants, interrelation with primary tumor location, and association with immune biomarkers in CRC. Methods: We retrospectively reviewed CRC tumors of all stages (with known sidedness) that underwent NGS with the Tempus xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq). Bivariate analyses were performed to compare KRAS alterations, immune biomarkers, and co-mutations by tumor location. P-values comparing individual co-mutations between groups were adjusted for false discovery (FDR). Results: A total of 3,391 CRC were analyzed (RT: n = 442 [13%], transverse: n = 116 [3%], LT; n = 2,833 [84%]) of which 1486 (44%) tumors harbored KRAS mutations. Overall, KRAS mutations were more frequent in RT compared to transverse tumors and LT (52% vs 41% vs 43%, p&lt;0.001, respectively). The most frequent KRAS mutation variants observed were G12D (29 %), G12V (22%), G13D (16%), and G12C (5.7%). There was no significant difference in the prevalence of KRAS variant types between LT and RT (p=0.5). Significant differences in genomic co-mutations with various KRAS variants were observed in the following genes: TP53, FBXW7, and NF1 (FDR- P&lt;0.05). RT and transverse tumors were more likely have MSI-H and TMB-H (&gt;10 mut/mb) status than LT (MSI-H: 18% vs 22% vs 2.2% and TMB-H (20% vs 22% vs 3%, P&lt;0.001), respectively. CRC tumors harboring G13D variants were more likely to be associated with and MSI-H and TMB-H status (and 7.7% and 8.5%) compared to G12D (2.8 % and 3.9 %), G12V (1.8 % and 2.1%), and G12C (0% and 2.4%); P = 0.003 and 0.001. Conclusions: The most frequent KRAS mutation variants observed in CRC tumors were G12D, G12V, G13D, and G12C. There was no significant difference in the prevalence of KRAS variant types between tumors of the left vs right colon. CRC tumors that harbored G13D variants were significantly more likely to be associated with MSI-H and TMB-H status. [Table: see text]
Identification and characterization of four bacteriome- and mycobiome-derived subtypes in tumour and adjacent mucosa tissue of colorectal cancer patients.
Authors: Manuela Salvucci, Liam Poynter, Reza Mirnezami, Steven Carberry, Robert O'Byrne, James Alexander, Diether Lambrechts, Kirill Veselkov, James M. Kinross, Jochen Prehn
Journal: Journal of Clinical Oncology (2023)

214 Background: The bacteriome and mycobiome, collectively referred to as the microbiome, is a key player in CRC pathogenesis, progression and response to chemotherapy, radiotherapy and immunotherapy. Microbial modulation and exacerbation in CRC is likely attributable to alterations of composition and diversity of the microbiome rather than to a single microbial species. We therefore systematically investigated alterations in the bacteriome and mycobiome of CRC patients in tumours and matched adjacent mucosa resulting in the identification of microbiome-based subtypes associated with host clinico-pathological and molecular characteristics. Methods: We estimated bacterial and fungal composition from RNA sequencing experiments using a validated subtractive method ( PathSeq) in in-house and publicly available cohorts. We evaluated the quality of the microbial estimates with two sets of orthogonal analysis determining i) the agreement with composition from an independent method and ii) retrieval of expected clinically-relevant microbial signatures. Diversity and composition of bacteriome and mycobiome of tumour and adjacent mucosa, and resulting subtypes were computationally deconvoluted using &gt; 10,000 samples. Results: The bacteriome of tumours had higher dominance and lower ɑ-diversity compared to matched adjacent local and distant mucosa. Tumours were enriched with Proteobacteria (Gammaproteobacteria class), Fusobacteria (including Fusobacterium Nucleatum species) and Basidiomycota fungi (Malasseziaceae family). Tumours were depleted of Bacteroidetes (Bacteroidia class), Firmicutes (Clostridia class) and Ascomycota (Sordariomycetes and Saccharomycotina). Tumours and adjacent mucosa samples were classified into 4 microbial subtypes, termed C1 to C4, based on the bacteriome and mycobiome composition. The bacterial Propionibacteriaceae, Enterobacteriaceae, Fusobacteriaceae, Bacteroidaceae and Ruminococcaceae along with the fungal Malasseziaceae, Saccharomycetaceae and Aspergillaceae were among the key families driving the microbial subtyping. Microbial subtypes were associated with distinct tumour histology and patient phenotypes and served as independent prognostic marker for disease-free survival. Key associations between microbial subtypes and alterations in host immune response and signalling pathways were validated in the TCGA pan-cancer cohort. The microbial subtyping demonstrated stratification value in the pan-cancer settings beyond merely representing differences in survival by cancer type. Conclusions: This study demonstrates the translational potential of microbial subtyping in CRC patient stratification, and provides avenues to design tailored microbiota modulation therapy to further precision oncology.
Early detection of pancreatic cancer using 5-hydroxymethylation profiles in plasma-derived cell-free DNA.
Authors: Anna Bergamaschi, David Haan, Micah Collins, Gulfem Guler, Melissa Peters, Lauren Gigliotti, Shimul Chowdhury, Wayne Volkmuth, Samuel Levy
Journal: Journal of Clinical Oncology (2023)

672 Background: Pancreatic cancer is one of the deadliest cancers, with approximately 15-20% of patients who present at diagnosis with a resectable disease. The major barrier to better outcomes is the lack of early-detection molecular tools to enable timely intervention. We have developed a test that enables the detection of pancreatic cancer from a simple blood draw. The test incorporates a novel, genome-wide sequencing-based epigenomics detection method that enriches for DNA loci that undergo active de-methylation. The measurement of 5-hydroxymethylcytosine (5hmC) provides a unique and stable biomarker for the early detection of cancer including pancreatic cancer. Methods: Whole-blood was obtained from a training cohort of 660 individuals (consisting of 132 pancreatic cancers (PaCa) and 528 non-cancers) and a validation cohort of 2,150 individuals (consisting of 102 PaCa and 2,048 non-cancers). Cell-free DNA (cfDNA) was isolated from plasma from which 5hmC and whole-genome libraries were generated and sequenced. Logistic regression algorithms were employed using 5hmC feature sets combined with physical characteristics of DNA fragments to optimally partition cancer from non-cancer samples. Results: Cross validation of the training model yielded an overall sensitivity of 65.9%,(95% CI, 57.2%–73.9%), early-stage (stage I-II) sensitivity of 57.1% (95% CI, 44%–69.5%) and a specificity of 98%. The model was further validated in a separate, non-overlapping set of blinded and independently processed samples and yielded an early-stage sensitivity of 68.3% (95% CI, 51.9%–81.9%) and a specificity of 96.9% (95% CI, 96.0%–97.6%). Conclusions: Our results demonstrate that plasma-derived cfDNA 5hmC profiles enable the accurate detection of early-stage PaCa, providing a valuable non-invasive tool especially for those individuals at high risk for the disease, including individuals with genetic predisposition and newly diagnosed type 2 diabetes. A larger clinical study (NODMED - NCT05188586) is ongoing and will provide clinical validation for the detection in individuals at high risk for this deadly disease.
Tumour radiomics as imaging biomarker of tumour response to chemo-radiotherapy in patients with adenocarcinoma of rectum.
Authors: Reena Engineer, Abhinav Puppalwar, Jayant Sastri, Ashish Jha, Suman Kumar, Avanish Saklani
Journal: Journal of Clinical Oncology (2023)

243 Background: We aimed to study whether texture (Radiomic) features obtained from T2W MRI of patients with rectal cancer can be used as a surrogate imaging biomarker to predict response to NACTRT. We explored various machine learning tools to develop the best model to predict response to NACTRT. Methods: One hundred patients with stage II/III who underwent MRI before and after NACTRT and surgical treatment were enrolled. Patients were classified into complete response (pCR, n = 21) and partial and nonresponse (pPR + pNR, n = 53) on the basis of histopathological report (74 patients who underwent surgery) and clinico-radiological response (26 patients who did not undergo surgery). Tumor volumes (Region of interest) were manually selected in each tumour segment. There were sixty four first-order and higher-order radiomic features. Recursive feature elimination method was used for feature selection and 5 prediction models were tested using 10-fold cross validation for predicting tumour response to NACTRT. Results: Using prediction model assessment matrix (RFC, SVC, GBC, NBC, ABC), the best results for prediction response were obtained using the random forest model with AUC of 0.79 ± 0.15 (Mean ± Standard deviation) accuracy of 0.72 ±0.12, precision of 0.77 ± 0.10, sensitivity of 0.87 ± 0.07, f1 score- 0.81 ±0.07. By using random forest model, Texrad features obtained from pre and post NACTRT MRI could accurately predict pCR. To the best of our knowledge, apart for the added values of RF model to Texrad features, is the first study to demonstrate and compare RF, SVC, GBC, NBC, Adaboost models to the same cohort of patient with 10-fold validation. Conclusions: Our study shows that RFM was most accurate and stable for predicting tumour response. MRI based Radiomic features can be used as surrogate image biomarker to accurately predict the treatment response to NACTRT in patients with locally advanced rectal cancer. The prediction model can be used as a complementary non-invasive tool to identify patients eligible for organ preservation. [Table: see text]
Effect of temperature on gastro-esophageal cancer outcomes: A SEER study.
Authors: Kush Gupta, Ashish Gupta, Anthony George, Kristopher Attwood, Shipra Gandhi, Beas Siromoni, Sarbajit Mukherjee
Journal: Journal of Clinical Oncology (2023)

467 Background: Cold stress suppresses antitumor response in animal models, leading to tumor growth . Recent studies have also shown a negative correlation between the average annual temperature (AAT) and cancer incidence. We hypothesized that esophageal cancer (EC) and gastric cancer (GC) patients living in warmer climates have improved overall (OS) and disease-specific survival (DSS) than those living in colder climates. Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database from 1996 to 2015. AAT at the county level was calculated based on the National Centers for Environmental Information. Cox multivariate regression models were performed to measure the association between temperature (measured continuously at diagnosis and in 5-degree increments) and OS/DSS, adjusting for variables. All associations were compared at a significance level of 0.05. The OS and DSS were summarized using Kaplan-Meier methods. All statistics were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). Results: A total of 17,408 EC patients were analyzed. The average age of the cohort was 65 years, 79% of which were male and 21% were female. Of them, 61.6% had adenocarcinoma, and 37.6% were squamous. After adjusting for covariates, patients in regions with AAT &gt;53.5°F had an 11% improvement in OS [HR 0.89 (95% CI 0.86-0.92), p&lt;0.0001] and 12% in DSS [HR 0.88 (95% CI 0.85-0.91), p&lt;0.0001]. When the temperature was analyzed in 5°F increments, with each increment, there was a 3% improvement in OS [HR 0.97 (95% CI 0.96-0.98), p&lt;0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95-0.97), p&lt;0.0001]. Subgroup analysis of squamous and adenocarcinoma showed similar results. These findings were validated in 20,553 GC patients. After adjusting for covariates, patients in regions with AAT &gt;53.5 had a 12% improvement in OS [HR 0.88 (95% CI 0.85-0.90), p&lt;0.0001] and 14% in DSS [HR 0.86 (95% CI 0.83-0.89), p&lt;0.0001]. When analyzed in 5°F increments, with each increment, there was a 4% improvement in OS [HR 0.96 (95% CI 0.95-0.97), p&lt;0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95 - 0.97), p&lt;.0001]. Conclusions: We showed for the first time that higher environmental temperatures are associated with significant improvements in OS and DSS in patients with gastro-esophageal cancer. Further confirmatory and mechanistic studies are required to implement specific interventional strategies.[Table: see text]
Anlotinib combined with paclitaxel and cisplatin as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC).
Authors: Gongqian Jiang, Guolei Wang
Journal: Journal of Clinical Oncology (2023)

409 Background: Preoperative chemoradiotherapy before esophagectomy in esophageal squamous cell carcinoma (ESCC) can obtain significant survival benefits for patients compared with surgery alone. The antiangiogenic drugs have shown efficacy in many cancers including esophageal cancer. The benefits of antiangiogenic drugs in neoadjuvant therapy for ESCC still worth exploring. Anlotinib was an effective second-line monotherapy for ESCC in China and the combination of anlotinib and chemotherapy might be a promising strategy as neoadjuvant treatment. Methods: This was a single-arm, non-interventional study. Patients diagnosed stage II-III ESCC confirmed by histopathology would be enrolled(N=30). Patients received neoadjuvant therapy with anlotinib (12 mg, po, d1-14, 21 days per cycle) combined with paclitaxel (135 mg/m 2 iv d1, 21 days per cycle) and cisplatin (60-75mg/m 2 iv d1, 21 days per cycle). The primary endpoints were pathologic complete response (pCR) rate, rate of R0 resection and disease-free survival (DFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety profile. Results: From July 2020 to September 2022, 20 pts (15 males and 5 females) were enrolled with a median age of 66 years (range: 48-75). 12 pts (60%) had ECOG PS 1, 8 pts had ECOG PS 2. 17/1/2 pts received 2/3/4 cycles of neoadjuvant treatment respectively. In best overall response assessment, ORR was 95% and DCR was 100%. Among them 18 pts underwent esophagectomy and all of them obtained R0 resection, as the rate of R0 resection was 90%. 6 pts (30%) were confirmed to be pCR. The median DFS was not yet available. The safety profile suggested that 3 (15%) pts occurred grade 1-2 treatment-related adverse events (TRAEs), including decreased leukocyte count (5%), diarrhea (5%), nausea and vomiting (5%). No grade ≥3 TRAEs were observed. Conclusions: The preliminary results of this study show promising efficacy and safety of anlotinib combined with paclitaxel and cisplatin as neoadjuvant therapy for patients with esophageal squamous cell carcinoma. More ESCC patients would be recruited in the future. Clinical trial information: ChiCTR2100054374 .